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Determinants of the thrombogenic potential of multiwalled carbon nanotubes.

ABSTRACT: Multiwalled carbon nanotubes (MWCNTs) are cylindrical tubes of graphitic carbon with unique physical and electrical properties. MWCNTs are being explored for a variety of diagnostic and therapeutic applications. Successful biomedical application of MWCNTs will require compatibility with normal circulatory components, including constituents of the hemostatic cascades. In this manuscript, we compare the thrombotic activity of MWCNTs in vitro and in vivo. We also assess the influence of functionalization of MWCNTs on thrombotic activity. In vitro, MWCNT activate the intrinsic pathway of coagulation as measured by activated partial thromboplastin time (aPTT) assays. Functionalization by amidation or carboxylation enhances this procoagulant activity. Mechanistic studies demonstrate that MWCNTs enhance propagation of the intrinsic pathway via a non-classical mechanism strongly dependent on factor IX. MWCNTs preferentially associate with factor IXa and may provide a platform that enhances its enzymatic activity. In addition to their effects on the coagulation cascade, MWCNTs activate platelets in vitro, with amidated MWCNTs exhibiting greater platelet activation than carboxylated or pristine MWCNTs. However, contrasting trends are obtained in vivo, where functionalization tends to diminish rather than enhance procoagulant activity. Thus, following systemic injection of MWCNTs in mice, pristine MWCNTs decreased platelet counts, increased vWF, and increased D-dimers. In contrast, carboxylated MWCNTS exhibited little procoagulant tendency in vivo, eliciting only a mild and transient decrease in platelets. Amidated MWCNTs elicited no statistically significant change in platelet count. Further, neither carboxylated nor amidated MWCNTs increased vWF or D-dimers in mouse plasma. We conclude that the procoagulant tendencies of MWCNTs observed in vitro are not necessarily recapitulated in vivo. Further, functionalization can markedly attenuate the procoagulant activity of MWCNTs in vivo. This work will inform the rational development of biocompatible MWCNTs for systemic delivery.

SUBMITTER: Burke AR

PROVIDER: S-EPMC3130101 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Determinants of the thrombogenic potential of multiwalled carbon nanotubes.

Burke Andrew R AR Singh Ravi N RN Carroll David L DL Owen John D JD Kock Nancy D ND D'Agostino Ralph R Torti Frank M FM Torti Suzy V SV

Biomaterials 20110612 26

Multiwalled carbon nanotubes (MWCNTs) are cylindrical tubes of graphitic carbon with unique physical and electrical properties. MWCNTs are being explored for a variety of diagnostic and therapeutic applications. Successful biomedical application of MWCNTs will require compatibility with normal circulatory components, including constituents of the hemostatic cascades. In this manuscript, we compare the thrombotic activity of MWCNTs in vitro and in vivo. We also assess the influence of functionali ...[more]

PMID: 21663954

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Project description:Currently, there is a lack of ultrasensitive diagnostic tool to detect some diseases such as ischemic stroke, thereby impacting effective and efficient intervention for such diseases at an embryonic stage. In addition to the lack of proper detection of the neurological diseases, there is also a challenge in the treatment of these diseases. Carbon nanotubes have a potential to be employed in solving the theragnostic challenges in those diseases. In this study, carbon nanotubes were successfully synthesized for potential application in the detection and treatment of the neurological diseases such as ischemic stroke. Vertically aligned multiwalled carbon nanotubes (VA-MWCNTs) were purified with HCl, carboxylated with H2SO4:HNO3 (3:1) and acylated with SOCl2 for use in potential targeting studies and for the design of a carbon-based electrode for possible application in the diagnosis of neurological diseases, including ischemic stroke. MWCNTs were washed, extracted from the filter membranes and dried in a vacuum oven at 60 °C for 24 h prior to functionalization and PEGylation. CNTs were characterized by SEM, TEM, OCA, DLS, CV and EIS. The HCl-treated CNT obtained showed an internal diameter, outer diameter and thickness of 8 nm, 34 nm and 75 µm, while these parameters for the H2SO4-HNO3-treated CNT were 8 nm, 23 nm and 41µm, respectively. PEGylated CNT demonstrated zeta potential, polydispersive index and particle size distribution of 6 mV, 0.41 and 98 nm, respectively. VA-MWCNTs from quartz tube were successfully purified, carboxylated, acylated and PEGylated for potential functionalization for use in targeting studies. For designing the carbon-based electrode, VA-MWCNTs on silicon wafer were successfully incorporated into epoxy resin for diagnostic applications. Functionalized MWCNTs were nontoxic towards PC-12 neuronal cells. In conclusion, vertically super-aligned MWCNTs have been successfully synthesized and functionalized for possible theragnostic biomedical applications in neurological disorders such as ischemic stroke.

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Determinants of the thrombogenic potential of multiwalled carbon nanotubes.

Publications

Determinants of the thrombogenic potential of multiwalled carbon nanotubes.

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